Increased expression of acidic mammalian chitinase in chronic rhinosinusitis with nasal polyps

BACKGROUND: Chitin is an abundant polysaccharide found in fungi, insects, and parasitic nematodes. Innate immune host defense against chitin-containing pathogens include production of chitinases. In human lower airways, acidic mammalian chitinase (AMCase) is produced in epithelial cells via a Th2-specific, IL-13-dependent pathway, and may act as an inflammatory mediator in asthma. The role of AMCase in chronic rhinosinusitis (CRS) has not been studied previously. METHODS: Eleven controls and 22 subjects with medically recalcitrant CRS were prospectively enrolled before undergoing endoscopic sinus surgery. RNA was extracted from surgically obtained ethmoid mucosa, and real-time PCR was used to determine expression of AMCase, eotaxin, and IL-13. Subjects were followed for at least 6 months postoperatively to assess for polyp recurrence. Based on the presence or absence of polyps, the subjects were classified as either recalcitrant or responsive to therapy. RESULTS: AMCase mRNA was detected in the sinus mucosa of 72% of control subjects and in 72% of patients with eosinophilic CRS with nasal polyps (CRSwNP). The expression of AMCase was significantly greater in recalcitrant CRSwNP than it was in treatment-responsive CRSwNP. There was no significant difference in IL-13 expression between these two groups. CONCLUSION: AMCase may be an important mediator in the pathogenesis of Th2 inflammatory diseases of the respiratory tract. Failure of medical and surgical therapy in CRSwNP is associated with significantly increased expression of AMCase, but not the Th2 cytokines IL-13 and eotaxin. Additional studies are needed to determine the potential of AMCase as a therapeutic target in CRSwNP.     

Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters

To assess the efficacy of an antibiofilm/antimicrobial agent combination, we incubated catheter segments colonized with one of six studied bacterial organisms in N-acetylcysteine, tigecycline, N-acetylcysteine-tigecycline, or saline. Segments were washed, sonicated, and cultured. N-acetylcysteine-tigecycline significantly decreased all viable biofilm-associated bacteria and was synergistic for methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.     

Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies

Purpose Capecitabine in combination with docetaxel given every 3 weeks has shown a high degree of activity in a number of tumor types, but at the expense of significant toxicity. To improve the therapeutic index, we evaluated a weekly regimen of docetaxel in combination with capecitabine, and determined the maximum tolerated dose, toxicities and pharmacokinetics of this combination.Patients and methods Patients with advanced solid malignancies were treated with docetaxel on days 1 and 8, and capecitabine, twice daily on days 1–14, of an every-21-day cycle. Pharmacokinetics of docetaxel were assessed on days 1 and 8 of the first cycle of chemotherapy.Results Enrolled in the study were 25 patients. The most frequent toxicities were asthenia, hand-foot syndrome and mucositis. Inability to deliver at least 75% of the planned doses of both drugs during the first two cycles of chemotherapy was noted at dose levels 2, 3 and 4. Dose level 1 (docetaxel 30 mg/m² and capecitabine 825 mg/m² twice daily) is the recommended dose for phase II studies. Five patients experienced a partial response, and eight patients had stabilization of disease. Coadministration of capecitabine did not alter the pharmacokinetics of docetaxel.Conclusion The regimen consisting of docetaxel 30 mg/m² (days 1, 8) and capecitabine 825 mg/m² twice daily (days 1–14) was well tolerated. Capecitabine did not alter pharmacokinetics of docetaxel. Further testing of this regimen in tumor-specific trials, especially gastric, lung and breast cancer, is warranted.Presented at the 39th Annual Meeting of the American Society of Clinical Oncology, May 2003, Chicago, IL.     

Laryngeal metastasis from a rectal carcinoma

Metastases to the larynx from distant primaries are rare. We report a case of a laryngeal metastasis from a rectal carcinoma.     

Effect of cell substrate on antioxidant enzyme activities in cultured renal glomerular epithelium.

The activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated guinea pig glomeruli and primary or subcultured glomerular epithelial cells. Cell injury was assessed by morphologic studies and by measurement of cellular lipid peroxidation (levels of malondialdehyde). Antioxidant enzyme activities were very different in cultured cells than in parent glomeruli. The possible effect of culture substrates (tissue culture plastic, bovine corneal endothelial [BCE] cell basement membrane, and PF-HR-9 endodermal cell basement membrane) on antioxidant enzyme status, cell morphology, and lipid peroxidation was also assessed. Glomerular epithelial cells cultured on the BCE cell basement membrane substrate survived longer and showed less lipid peroxidation than cells cultured on plastic or the HR-9 substrate. Cells cultured on a plastic substrate had substantially less glutathione peroxidase activity than cells cultured on either BCE or HR-9 basement membranes.     

Utility of hepatobiliary scintigraphy in diagnosing or excluding biliary atresia in premature neonates and full-term infants with conjugated hyperbilirubinemia who received parenteral nutrition

Purpose: Hepatobiliary scintigraphy (HBS) is used to aid in the diagnosis of Biliary Atresia in full-term infants with conjugated hyperbilirubinemia. There is little information on the utility of the HBS in premature infants with conjugated hyperbilirubinemia and infants with parenteral nutrition associated cholestasis (PNAC). The purpose of this study is to assess the utility of HBS in differentiating Biliary Atresia and PNAC in premature neonates and full-term infants who received parenteral nutrition (PN).

Materials and methods: Retrospective data collection and analysis on infants who developed conjugated hyperbilirubinemia and had HBS performed during their stay at level IV neonatal intensive care unit between 2005 and 2015.

Results: A total of 20 patients with exposure to PN had HBS; two patients were confirmed to have Biliary Atresia. There were no statistically significant differences between patients with Biliary Atresia versus PNAC in demographics, days on PN, or gamma glutamyl-transferase levels. Stool color was statistically significantly different between the two groups; patients with Biliary Atresia had acholic stools more consistently than patients without Biliary Atresia. HBS had 100% sensitivity, 17% specificity, positive-predictive value of 12%, and a negative-predictive value (NPV) of 100%.

Conclusions: These data indicate that the ability of HBS to aid in diagnosing Biliary Atresia is poor in a population of preterm neonates and full-term infants with PNAC. Although there is 100% sensitivity, the poor specificity (17%) should be acknowledged when utilizing HBS to diagnose Biliary Atresia in this vulnerable patient population. NPV of 100% is helpful in ruling out Biliary Atresia in this population.     

Tuberculous meningitis

Summary In a five-year-period, 288 cases of tuberculous meningitis were seen in in the R.M. & T.M.C. hospitals, Thanjavur, Tamilnadu. 87 children died. Of 215 cases discharged as relieved, only 117 cases were followed up. The period of follow up varied from 6 months to over 3 years. 41 children were followed up for more than 1 year. 47 children were found to have residual sequelae. The most frequent sequelae were mental retardation, seizures, generalised rigidity and spastic hemiplegia. From the Department of Pediatrics, Thanjavur Medical College, Thanjavur, Tamilnadu     

Circulatory congestion in obese hypertensive women: a subset of pulmonary edema in pregnancy

We describe four obese, chronically hypertensive women presenting with antepartum pulmonary edema in whom invasive hemodynamic monitoring showed elevated wedge pressure, normal to high cardiac index, and normal systemic vascular resistance. Echocardiography revealed large chambers, thick walls, and increased left ventricular mass with normal systolic but abnormal diastolic function. These findings are indicative of intrinsic volume overload occurring in the presence of impaired left ventricular relaxation, a combination resulting in high filling pressures and pulmonary congestion. Diuretic therapy is indicated in this subset of patients, who could not be recognized by the usual clinical parameters such as history and physical examination, chest x-ray, and arterial blood gas.     

Neuromuscular transmission studies in preeclamptic women receiving magnesium sulfate

The purpose of the study was to evaluate the neuromuscular transmission defect in preeclamptic women receiving intravenous magnesium sulfate and to study the correlation of the degree of defect with serum magnesium and calcium levels. The study population included: group 1, 14 preeclamptic women receiving magnesium sulfate and undergoing induction of labor; group 2, six preeclamptic women studied in the postpartum period while receiving magnesium sulfate; and group 3, 10 normotensive women undergoing induction of labor. The neuromuscular transmission studies were performed with standard techniques before and during the administration of magnesium sulfate. During magnesium sulfate therapy patients in groups 1 and 2 showed abnormal responses characterized by an initial low-amplitude muscle action potential followed by a progressive increase in the amplitudes of the successive responses. There was significant correlation between the degree of the neuromuscular transmission defect and serum magnesium levels, serum calcium levels, and the magnesium/calcium ratio in groups 1 and 2. All studies were normal in group 3. The findings confirm the occurrence of abnormal neuromuscular transmission in preeclamptic women receiving magnesium sulfate, and the intensity of the defect correlates significantly with increased serum magnesium levels and decreased serum calcium levels.